Interferon treatment of AKR,C cells was followed by the establishment of an antiviral state and apparently concomitant morphological, physical, and biochemical alterations of the cell plasma membrane. The density of the plasma membrane was significantly altered, and the concentration of some plasma membrane glycoproteins, and the number of intramembranous particles observed in freeze-fracture electron micrographs were increased. A parallel increase in the concentrations of intramembranous particles and the resistance to viral infection during interferon treatment as well as their parallel removal of interferon was suggestive of a relationship between the particle density and the establishment of the antiviral state.